The active substances ursodeoxycholic acid (UDCA) and the associated diastereomer chenodeoxycholic acid (CDCA), inter alia, have been employed for many years for the medicinal treatment of gallstones. Both compounds differ only by the configuration of the hydroxyl group on the C atom 7 (UDCA: β-configuration, CDCA: α-configuration). In the prior art, various methods for the production of UDCA are described, which are carried out purely chemically or consist of a combination of chemical and enzymatic process steps. The starting point is in each case cholic acid (CA) or the CDCA produced from cholic acid.
Thus the classic chemical method for UDCA production can be represented schematically as follows:

A serious disadvantage, among other things, is the following: since the chemical oxidation is not selective, the carboxyl group and the 3α and 7α-hydroxy group must be protected by esterification.
An alternative chemical/enzymatic method, based on the use of the enzyme 12α-HSDH is described, for example, in the PCT/EP2009/002190 of the present Applicant. In particular, recombinantly produced 12α-HSDH is employed here. The enzyme is preferably produced here by recombinant E. coli hosts, isolated therefrom and employed for reaction.
The 12α-HSDH oxidizes CA selectively to 12-keto-CDCA here. The two chemical protection steps necessary according to the classic chemical method are unnecessary here.
It is problematic in this method that the valuable product UDCA produced in this way is contaminated for reasons unknown up to now with lithocholic acid (LCA).
Novel 7β-HSDHs and use thereof in the production of UDCA in the reductive route are described in the PCT/EP2010/068576 of the Applicant. It is problematic here that the recombinant E. coli hosts also produce endogenous 7α-HSDH, and the 7α-HSDH produces a 3,12-diketo-CDCA by-product from dehydrocholic acid. This 3,12-diketo-CDCA is then no longer a substrate of the 7β-HSDH, so that in addition to the desired product the undesired by-product is also accumulated.
The object of the invention is therefore the provision of a novel method for the production of UDCA, which avoids the disadvantages described above. In particular, the enzymatic/chemical production of UDCA without impurities, such as LCA or 3,12-diketo-CDCA, is to be made possible.